β-Estradiol attenuate amyloid β-peptide toxicity via nicotinic receptors

A number of epidemiological studies suggest that estrogen therapy is linked to a reduced risk of developing Alzheimer's disease (AD). The present study was conducted to evaluate the effect of 17 beta-estradiol on beta-amyloid (A beta)-induced toxicity and was performed in rat pheochromocytoma PC 12 cells by measuring the mitochondrial activity. 17 beta-Estradiol (10(-5), 10(-6) and 10(-8) M) attenuated A beta(25-35)-induced toxicity in PC 12 cells. The neuroprotective effect of 17 beta-estradiol (10(-5) M) was prevented in the presence of the nicotinic antagonists methyllycaconitine (MLA) and mecamylamine, suggesting an interaction probably via the alpha 7 nicotinic receptor subtype. Chronic treatment with 17 beta-estradioi (10(-10)-10(-5) M) alone did not change the number of [H-3]epibatidine binding sites in human neuroblastoma SH-SY5Y cells and rat PC 12 cells, but significantly prevented the enhanced [H-3]epibatidine binding in nicotine-treated PC 12 cells. This study demonstrates that 17 beta-estradiol exerts neuroprotective effects which might involve interaction with the alpha 7 nicotinic receptor subtype. (C) 1999 Lippincott Williams & Wilkins.